This invention relates to cell adhesion systems, and more specifically to cells having increased cell adhesion properties.
The adhesion of cells to extracellular matrix components appears to be fundamental in cell behavior patterns such as cell division, cell differentiation, and embryonic cell migration and sorting. Moreover, certain abnormal cell behaviors, such as tumor invasion and metatasis, may result from alterations in the mechanisms of adhesion of cells to the extracellular matrix.
Cell adhesion appears to be mediated largely by cell surface receptors which recognize and specifically bind to cell adhesion-promoting molecules, or ligands, in the extracellular matrix. A number of such adhesion-promoting molecules have been identified including fibronectin, vitronectin, laminin and the collagens. It is now recognized that various of these adhesion-promoting molecules share the amino acid sequence arginine-glycine-aspartic acid (-Arg-Gly-Asp or RGD) which functions as the cell-binding domain and accounts for the ability of cells to recognize and bind to these molecules.
Adhesive cells exhibit a number of different types of RGD-directed receptors on their surfaces, the proportion of which is specific to the cell type. Although these receptors all bind to the RGD-containing domain of their ligand, they nonetheless exhibit specificity to their particular cell-adhesion promoting molecule. Synthetic peptides containing the RGD sequence can be used to promote cell adhesion when coated on a substrate or to inhibit cell attachment when presented in soluble form.
Because the ability to bind to extracellular matrix components resides in the cell-surface receptors, the degree of cell adhesion should be affected by quantitative changes in the number of receptors present on the surface of the cells. A method to provide cell lines having enriched levels of receptors would be of considerable utility in providing cells which would exhibit increased binding ability and would provide a particularly useful source of cell surface receptors. Moreover, such a method may be useful for increasing the number of receptors in abnormal cell lines whose pathology results from a lowered number of receptors or in normal cell lines which have dedifferentiated as a result of a lowered number of receptors. The present invention satisfies these needs and provides related advantages as well.